Human cells contain singular DNA repair pathways to excise critical lesions from DNA. In individuals with clinical syndromes predisposing to malignancy, the capacity to excise these lesions is impaired. This research proposal is designed to investigate the ability of human cells to actively regulate DNA repair pathways as they traverse the cell cycle. In particular, we seek to determine whether normal human cells modulate the pathway for nucleotide excision repair or the pathway for base excision repair as they are synchronously stimulated to proliferate. Further, we seek to examine whether the regulation of singular DNA repair pathways are defective in cells from individuals with clinical syndromes predisposing to malignancy. The objectives of this proposal are: 1) to characterize the induction of nucleotide excision repair and of base excision repair in synchronous populations of WI-38 cells stimulated to enter the cell cycle. 2) to determine the sequence with which normal human cells enhance the potential for DNA repair with respect to the induction of DNA replication. 3) to determine whether the failure of repair defective human cells to excise critical DNA lesions can be causally related to their inability to regulate those DNA repair pathways responsible for the excision of those lesions.